Immune checkpoint inhibitors and rheumatoid arthritis: All roads lead to PD-1?

Immune checkpoint molecules like PD-1 and its ligand PD-L1 and CTLA-4 are important regulators of the immune system. Medications blocking these pathways, immune checkpoint inhibitors, have been used to treat a variety of malignancies, while drugs agonizing these pathways, like abatacept, have been used in treating autoimmune diseases. Modulation of the PD-1/PD-L1 axis has become important for rheumatologists to understand in several different clinical scenarios. Currently, PD-1 agonists are being developed for treatment of rheumatoid arthritis (RA). In addition to patients with RA being potentially treated with PD-1 agonists, patients with rheumatoid arthritis may be treated with anti-PD-1/PD-L1 immune checkpoint inhibitors if they develop cancer. Finally, patients treated with immune checkpoint inhibitors may develop de novo inflammatory arthritis and be referred to rheumatology for management. In all three scenarios, there remain many unanswered clinical and translational questions. The parallel development of therapeutics antagonizing and agonizing the PD-1/PD-L1 pathway presents a unique chance for discovery in inflammatory arthritis.